On August 28, 2017, fulvestrant (Faslodex) was approved at 500 mg as monotherapy for expanded use in postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer who have not received previous endocrine therapy.1

Supporting Efficacy Data

Approval was based on improved progression-free survival in the phase III FALCON trial, in which 462 postmenopausal women with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who had not received any hormonal therapy were randomized to receive fulvestrant at 500 mg by intramuscular injection on days 1, 15, 29, and every 28 days thereafter (n = 230) or daily oral anastrozole at 1 mg (n = 232).1,2 The median age of patients was 63 years; 87% had metastatic disease; 55% had visceral metastasis; 17% had received one prior chemotherapy regimen for advanced disease; 84% had measurable disease; and the sites of metastases were musculoskeletal in 59%, lymph nodes in 50%, lungs in 40%, and liver (including gallbladder) in 18%.

The growth of estrogen receptor–positive breast tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the estrogen receptor protein in human breast cancer cells. Studies in vitro showed that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant and estrogen-sensitive human breast cancer (MCF-7) cell lines. In tumor studies in vivo, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts.

How It Is Used

As monotherapy, the recommended dose of fulvestrant is 500 mg given intramuscularly into the buttocks (gluteal area) slowly (1–2 minutes per injection) as two 5-mL injections, one in each buttock, on days 1, 15, 29, and once monthly thereafter. In patients with mild hepatic impairment, the recommended dose is 250 mg (one 5-mL injection) on the same schedule. Fulvestrant has not been evaluated in patients with severe hepatic impairment.

Safety Profile

In the FALCON trial, the most common adverse events of any grade in the fulvestrant group were arthralgia (17% vs 10% in the anastrozole group), hot flash (11% vs 10%), fatigue (11% vs 7%), and nausea (11% vs 10%). The most common grade ≥ 3 adverse events were back pain (one vs zero patients) and fatigue (one vs one patient). Adverse events led to discontinuation of study treatment in 1.8% vs 1.3% of patients, with reasons in the fulvestrant group including drug hypersensitivity (0.9%), injection-site hypersensitivity (0.4%), and elevated liver enzymes (0.4%). The most common grade ≥ 3 laboratory abnormalities were increased aspartate transaminase (1.3% vs 0.4%) and increased alanine transaminase (1.3% vs 0%).

Fulvestrant Monotherapy

Fulvestrant (Faslodex) was approved at 500 mg as monotherapy for expanded use in postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer who have not received previous endocrine therapy.

As monotherapy, the recommended dose of fulvestrant is 500 mg given intramuscularly into the buttocks slowly as two 5-mL injections, one in each buttock, on days 1, 15, 29, and once monthly thereafter.

Fulvestrant carries warnings/precautions for the risk of bleeding, increased exposure in patients with hepatic impairment, injection-site reaction, embryofetal toxicity, and immunoassay measurement of serum estradiol (fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels). Fulvestrant should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. Caution should be used while administering fulvestrant at the dorsogluteal injection site due to proximity of the underlying sciatic nerve. Fulvestrant is contraindicated in patients with known hypersensitivity to the drug or any of its components.